N-carboanhydrides of alpha amino acids and polyamides



ing, alpha-amino acid polyamides.

Patented Aug. 26, 1952 N-CARBOANHYDRIDES OF ALPHA AMINO ACIDS AND POLYAIWIDES Charles W. Tullock, Wilmington, Del., assignor to E. I. du Pont de Nemours and Company, Wilmington, DeL, a corporation of Delaware No Drawing. Application June 17, 1949,

Serial No. 99,853 7 Claims. (Cl; 260-78) This invention relates to new condensation polymers. More specifically it relates to new alpha-amino acid polyamides.

Curtius, J. prakt. Chem. 125, 211-302 (1930) reported the preparation of the N-carboanhydride of DL-norvaline (alpha-amino-n-valeric' acid) by a complicated procedure involving the preparation of n-propylmalonic azide acid and itssubsequent thermal decomposition to a purported mixture of the N-carboanhydride and the polymeric anhydride of alpha-amino-n-valeric acid. This report is, however, erroneous, since the N-carboanhydride of DL-norvaline (prepared by the reaction of DL-norvaline with phosgene in anhydrous diethyl ether) is a white crystalline material melting at 66 C. instead of the 161 C. reported by Curtius. The polymer prepared therefrom, e. g. by the methods of MacDonald Ser. No. 778,031 and Ser. No. 778,032, filed October 24, 1947 and Ser. No. 766,457, filed August 5, 1947, gives a white, high molecular weight polymeric norvaline, whereas the material reported by Curtius to be a norvaline polymer is a yellow brown vitreous brittle polymer. This polymer is of a low degree of polymerization.

High molecular weight filmand fiber-iormin polymers can be prepared from the N-carboanhydrides of norvaline and norleucine. These polymers, especially the hcmopolymers, exhibit relatively high organic solvent resistance, making them especially useful in the formation of films and fibers destined for long-term exposure to organic solvents, such as for instance those normally used in the dry cleaning industry. Although these polyamides are of interest for their high organic solvent resistance, this same property makes them less easily adaptable to normally used techniques of film-casting and fiber-spinning from solution.

This invention has as anobject the preparation of high molecular weight, filmand fiber-form- A further object is the preparation of high molecular weight, filmand fiber-forming polymers havin high insolubility in a wide range of organic solvents, buthaving suiiicient solubility in other solvents to allow their use in conventional filmand fiber-forming procedures and techniques.

Another object is the preparation of N-carboanhydrides of alpha-amino acids suitable for the preparation of such polymers. Other objects will appear hereinafter.

prylic) acids and the high molecular weight, filmand fiber-forming polyamides prepared therefrom by condensation, with carbon dioxide evolution. These polymers exhibit relatively high insolubility in a rather wide range of organic solvents but are sufficiently soluble in' other selected organic solvents to make them easily usable in normal filmand fiber-forming operations from solution.

The N-carboanhydrides of alpha-amino-nheptanoic and alpha-amino-n-octanoic acids, 1. e., the N-carboanhydrides of 7 and 8 carbon straight chain alpha primary aminoalkanoic acids, 1. e., the N-carboanhydrides oi aminoacetic acids carrying a 5 to 6 carbon straight chain hydrocarbon substituent on the alpha-carbon atom are characterized by ready solubility in clioxane, diethyl ether and benzene and easy recrystallizability from diethyl ether/petroleum ether mixtures. They are white, crystalline, lowmelting solids (SQ- C.) which evolve gas at relatively low temperatures close to the melting point (-108 C.).

The term inherent viscosity, or 1 an. as used herein is defined by the following equation: I

wherein Zn represents the natural, or Napierian, logarithm, C is concentration of the solute in grams/ cc. of solution and 1; solution 77 1 solvent 77 being viscosity.

The following examples in which partsare, by weight are illustrative of the invention.

EXAMPLE I Preparation of alpha-amino-n-heptanoic "acid N-carboanhydride 65' that an excess of phosgene overithe theoretical and: 86 parts of petroleum ether.

3 amount required is added. The resulting, clear, colorless solution is concentrated to approximately l2.5-15% of its volume through removal of most of the dioxane by distillation at 4652 C. under reduced pressure (15-16 mm. of mercury) over a'period. of. 70 minutes. The syrup remaining is extracted twice with 66 part portions of petroleum ether. The oil remaining is then dissolved in 35.4 parts of anhydrous diethyl ether and 145 parts of petroleum ether added to the cloud point. Upon cooling the resultant cloudy solution in ice and water until no :furtherpre cipitate crystalizes and subsequently removing. the white crystalline material by filtration there is obtained 19 parts (53.6% of theory) of slightly impure alpha-amino-n-heptanoic acid N-carboanhydride. An additional parts of the slightly impure N-carboanhydride is isolated by concentrating the mother liquor from the previous crystallization under vacuum. These portions of theN-carboanhydride are combined and recrystallized from 71 parts of anhydrous diethyl ether After cooling the --recrystalliza-tion solution until no further precipitate: forms and removing the white crystalline material byfiltration, there is thus obtained 19.5 parts (55% of theory) of-the' pure N- carboanhydride of alpha-amino-n-heptanoic acid as white needles melting at 59-60 C. and evolving .sasat. 108 C.

ANALYSIS Calculated. for CaH-iaOsNE. C, '56 .14 %I'; H', 7560 N... 8.18%. Found: C}. 56.35%: H; 7.73%; N,

EXAMPLE II.

: Brepamt'ion of the linear polyamide of alpha.-

aminor-n-heptanoz'c acid Twoparts "ofthe aboveN-carboanhydride of alpha-amino-n-heptanoicacid dissolved in 88 parts of reagent benzene co'ntaining water butin amount less than 0.02 per cent, is heated at-65 C.

in"'a'rea'ctor operate the atmosphere-through a small capillary tube for 93.6 hours. of this time the solution, while still fluid, has become appreciably more-viscous and exhibits a blue fluorescence. A portion of the polymerizationsolutionls poured'onto a glass casting surface and the benzene allowed toevaporateslowly at room temperature: There'is' thus obtained, after removal fromthe casting surface, a clear, self-supporting filmof'thepclyamide of alphaamino-n-heptanoic acid. This polyamide, while soluble in benzene as indicated, is insoluble in meta-'creseljchloroform, and 298-1007.; formic acid.

EXAMPLEIII .--.Preparati0n: of. aZpha-amino-n-octanoz'c. acid.

' N-carboanhydridc Assuspension'of 50' parts of alpha-amino-n- At the end '4 starting amino acid) of alpha-amino-n-octanoic acid hydrochloride. The dioxane is removed from the clear filtrate by distillation at 4555 C. under reduced pressure (5 mm. of mercury) over a period of 2.3 hours. The solid residue is dissolved-in 424.8. parts of. anhydrous diethyl ether and 325 parts ofpetroleumether added. The resulting mixture is allowed to stand at room temperature for 0.5 hour, and'the solid crystalline material that precipitates is removed by filtration. There is thus obtained 34 parts (58.5% conversion and 60.5% yield) of alpha-amino-noctanoic acid. N-carboanhydride. Thirty-four parts .of this product is dissolved in 516.8 parts of anhydrous diethyl ether and 316.8 parts of petroleum ether added. The resulting solution is cooled to 0 C. and the solid product that precipitates is removed by filtration. There is thus obtained 21 parts (61.8% recovery) of pure alphaamino-n-octanoic acid N-carboanhydride as a white,.fiuffy, crystalline. solid melting at 78-80 C.

ANALYSIS Calculated for CsHi'sOsNi 0.584%; 8. 1%. Found C 58.5%; H, 8.2

EXAMPLE .IV

Preparation of the linear poly mide of alphadmin'o-nwctan'oic acid Two parts of theabove alpha-amino noctanoic acid N-carbo'anhydride are polymerized'by heating in 44 parts of reagentgrade benzenefor three days at 65 C. in a-reactor openlto the atmosphere through a small capillary tube. The resulting, clear, viscous solution is poured in a thin film onto a-glass plate and the'ben'zene solvent allowed to evaporate at" room temperature. After removal from the casting surface there is'obtained a clear film of the polyamide of alph'a a'mino-n-octanoic acid. This polyamide' is-a-lmost completely soluble in chloroform and insoluble in meta-c'resol and formic acid. It is cold-drawable and exhibits at the break a tensile strength of l2-8 3 -lb./ sq. in. and 46% elongation.

EXAMPLE V Prep ration of" the copolya'mz'de from (r- 1:1 by weight "mixture 07" the N-carboanhydi'ides of alpha-amino-n-octanoic acid and DL-Zeucme A mixture of equal parts of the N-carboanhydrides of alpha-amino-n-octanoic acid and DL- leucine: is polymerized by heating in 44 par-ts of reagent grade'benzene for six daysat 65 C. in a reactor open to the atmosphere through a small capillary tube. At the end of this time 37.2 parts of chloroform is added to the clear viscous polymer solution. The resulting. solution is thoroughly mixed by gentle warming and stirring and subsequently flowed in a thinfilm onto a glass plate and the solvents allowed to evaporate-at room temperature. After removalfrom the casting surface there is obtained a clear, strong film of the copolyamide from a lzLby weight mixture of the N-carboanhydrides of .alpha-amino-n-octanoic acid and .DL-leucine.

This film is readily soluble in meta-cresol and chloroform. It is orientable, drawing about 200% at 240 C. to-give a much stronger film. The inherent viscosity of the copolyamide at 0.1

. and 0.3% concentrations (i. e., 0.1 g./ cc. of solution and 0.3 g./l00 cc. of solution) in metacresol is 0.88 and. 0.89, respectively.

VI Preparation of fliecopolyamid from a 1:1 by weight mizrtureof thaN-carboaznhydrides Qf laZpha-amino-n-octanoic acid and" lpha-am no-n-batyrz'c acid .1 A mixture of equal parts of the N-carboanhydrides of 'alphaeamino-n-octanoic acid and alpha-amino-n butyric acidis dissolved in 66 parts ofvreagent grade benzene and heated at -65C$for six days in aireactoropento the at- ;mosphere only through'a capillary tube. During the polymerization the copolyamide'in the form chloroform. 1

Although in the foregoing examples certain conditions of reaction such as time, temperature,

proportions, etcyhave been given for the preparation of thenovel -Ncarboanhydrides of this in- .vention it is'to be understood that other methods known in. the art for preparing N-carboanhydrides' can alsobe used; Thus, the N-carboanhydrides of this invention can be prepared, as

is disclosed in the copending application of Prichard, filed October 7, 1947, Ser. No. 778,457, by treating an alpha-amino acid'in an anhydrous solvent with an alkali metal alkoxide and with carbon dioxide thereby forming the dialkali metal salt of the alpha-carboxyaminocarboxylic acid and reacting thionyl chloride with this salt and isolating .the desired N -carboanhydride.

The novel N-carboa'nhydrides of this invention can also be'prepared, asis disclosed in the copending application of MacDonald, filed March 24, 1949, Ser. No. 83,299, by reactingthe requisite amino acid orit's alkali metal or alkaline earth metalsalts with phosgene under anhydrous conditions. The novel. N-carboanhydrides of this invention also canbe prepared by the'meth- 0d disclosed in ,the. copending application of Prichard,,,filed October 5, 194B, Ser. No. 52,971,

by reacting the requisite amino acid or its alkali metal, alkaline earth metal, or hydrohalide salts with phosgene under. anhydrous conditions and in the presence ofan ether, as is illustrated by Examples I and III. c

The novel N'-carboanhydrides of this invention ,canal'so be prepared from the corresponding amino acids as.reportediby'Leuchs, Ber 39,857 (1905), by reacting the amino acidwith a-chloroformate' ester, isolating the ester of the N- cai box'yamino acid so formed and subsequently reacting this derivative with thionyl chloride under anhydrous conditions and isolating the desired N-carboanhydrides.

,The present-invention is generic to the N- carboanhydrides' of alpha-primary-amino acids of the following type formula:

cnewnon-on coon Inn,

'wherein n is aninteger of from 4 to 5. Of these N-carboanhydrides that form the amino acid of "the above-given"formulawherein n is 5, i. e.,

alpha-amino-n-octanoic acid, is preferred since i the amino acid and also the N-carboanhydride are preparable from a readily available intermediate,namely, n-heptaldehyde which is available in good yields by the destructive distillation of castor oil under reduced pressure (see page 247, Whitmore, "Organic Chemistry, Van Nostrand, 1937). This N-carboanhydride is also preferred since the polyamides prepared therefrom are in general somewhat more soluble, especially in benacne and chloroform, than the corresponding products from the alpha-amino-n'heptanoic acid making them easier to handle in conventional procedures. Furthermore, polyamides prepared from this preferred N-carboanhydride are in general slightly superior in physical properties such as tensile strength and elongation and in addition more easily obtained in higher molecular weights as evidenced by the fact that they are more readily cold-drawable, i. e., orientable.

This invention is also generic to the polymers from the above-mentioned N-carboanhydrides. These polymers are linearcondensation polyamides and consist of recurring alpha-primary monoaminomonocarboxylic acid units 10 to of which are units of the following formula wherein n is an integer of from 4 to 5 7 When at least 10% of the recurring units of the polyamides of this invention arecomposed of the residues of amino acids of the above-given formula,improvements over the corresponding polymers containing less than 10% of the residues of amino acids of the above-given type for mula are noted in the above-mentioned combination of unique properties, i. e., relatively high insolubility in a rather Wide range of organic solvents, but suilicient solubility in other selected organic solvents to perm t easy usage in normal filmand fiber-forming operations from solution, relatively high thermal resistance, desirable softness and pliability coupled with adequate tensile strength and resistance to marring. For instance, polyamides from the straight-chain alpha-primary-monoaminomonocarboxylic acids containing 5 and 6 carbon atoms, i. e., norvaline and norleucine, are highly resistant to' most organic solvents especially in the cases of the homopolymers; Conversely, polyamides from the straight-chain alpha-primary-monoaminomonocarboxylic acids containing 12 and" 14 carbon atoms, 1. e., alpha aminolauric and alpliaaminomyristic acids, are easily soluble in organic solvents, even in such typical non-solvents for alpha-amino acid polyamides as diethyl ether and petroleum ether. The polyamides of this invention are generally soluble in "benzene orc'hlforobenzene in sufiicient concentrations to allow the preparation of films and fibers and are variously insoluble in In-cresol, chloroform, formic acid and other good organic solvents. i The polyamides of this invention are softer and morepliable in general than the alpha-amino acid polyamides irom branched-chainalpha-primarymonoaminomonocarboxylic acids, for instance, synthetic, optically inactive alpha-aminoisocaproic acid. They-arealso generally resistant to temperatures as high as 350 C. exhibiting nn melting and only slight browning, whereas polyamides from alpha-aminolauric and alpha-amino1nyristic acids exhibit sticl; temperatures in the range 250-260 C. and melt with decomposition above .325-330" C.

As the proportion of the residues of amino acid of this type in the polymers of this inven- 7 tion increases there is a corresponding increase in the aboveem'entioned desirable properties. This becomes particularly noticeable when the polymers contain a major proportion, i. e.,..more Jthan 50%. and preferably more than 70% of units of the above described amino acids.

In the case of copolymers containing the residues of other types of alpha-amino acids there will be, of course, additional units in the polymer. chain. However, upon hydrolysis with hydrochloric acid, all polymers of this invention yield *ahydrolysis product consisting of alphaamino .carboxylic acids (as the hydrochlorides) atleast (10% .of which consists of at least one alpha -primarymonoaminomonocarboxylic acid ofzthe general formula oHu oHiMOH O o 0'13 NHZ Whereinm isan integer from 4 to 5.

The N-carboanhy-drides of this invention, of

the iormula where n is an integerfrom 4 to '5, may be copol- .ymerized with the N-carboanhydride of any alphae-monoaminomonocarboxylic acid including, in addition to those specified above, alphaprimary aminoalkanoic acids, e. g. alanine, isoleucine, alpha-methyl-alpha-amino n butyric acid, glycine, alpha-aminolauric acid, alphaaminomyristic acid, alpha-aminoisobutyric acid, 2-'amino-4,6,6-trimethylheptanoic acid; cycloaliphatic alpha-primary :aminocarboxylic acids, e. g; 1-aminocyclopentanecarboxylic acid, .1- aminocyclohexanecarboxylic acid, l-amino-cycloheptanecarboxylic acid; hydrocarbon-substituted alpha-primary aminoalkanoic acids, e. g. phenylalanine; N -aryl-substituted alpha-secondary aminocarboxylic acids, e. g. N-phenylglycine; N-alkyl-substituted alpha-secondary aminocarboxylic acid, e. g. N-met-hylglycine, N-isopropyleucine.

The polyamides and copolyamides of this invention are prepared, optionally in the presence of inert organic liquids (particularly those free from active hydrogen), by the condensation- ;polymerization with carbon dioxide evolution (initiated thermally or by water, alcohols, phenols, organic acids, or amino hydrogencontaining amines of the previously defined alpha-amino acid N-carboanhydrides. Suitable organic liquids that can be used include aromatic hydrocarbons, e. g., benzene, xylene; halogenated hydrocarbons, e. g, chloroform, chlorobenzene, carbon tetrachloride; alicyclic ketones,

e. g., cyclohexanone; and ethers, e. g., anisole or dibutyl ether.

The N-carboanhydrides are suitably heated,

in a vessel adapted to permit the escape of -in-the mixture to be polymerized. The time of the reaction can be shortened or the temperature can be lowered or both can be accomplished by the use of reaction initiators, e. g., water, alcohols, lphe'nols, organic acids, or amino hydrogen- 8 containing amines. Heating at 65 C. for 24 to 144 hours is effective. Temperatures of -200 C. are used when no solvent is employed;

' The polyamides' and c'opolyamides of this invention can be used to produce 'fi'hnsand fibers. They also can be used in molding and coating compositions. These polyamides are suitable in one or more of the following uses; sutures, bandages, wrapping foils and the like.

The polyamides of this invention are characterized by a unique combination of properties, as above indicated. They differ markedly from other alpha-amino acid polyamid'es previously knownin the art. For instance;.alpha-amino acid polyami-des containing norvaline and norleucine units form rather stifi films andfibers, tending to be brittle and to exhibit a hard, glossy, slippery finish. vI-n -contrast,.the polyamides of thisinventiomsi. -e., those containing more than 10% and preferably more-than 50% "combined alpha-amino-n-heptanoic and/or alpha-aminm 'n-octanoi'c acid residues, form films andfifibers which are noticeably more pliable and whose surface is softer and less glossy.

Furthermore, the polyamides from shorter branched chain alpha-amino acids, e, g., alphaaminoisocapr'oic acid, as disclosed in the copending application of Cleaver and Schreiber, filed January 19, 1949, Ser. No. 71,756, although exhibiting excellent strength and toughness are not as soft and pliable as is desired. The poly amides of this invention although not as strong as the. polyamides from shorter, branched chain alpha-amino acids, are appreciably softer. and more pliable-properties much desired for the preparation ofiilms and fabrics of good feel and hand.

, The polyam-ides .from' the shorter 'ch'ain alphaamino acids, as discussed; "for example, in the above-identified application of Cleaver and Schreiber and in the various 'copending applications of MacDonald previously mentioned in'thi's specification, while tough and strong, not only tend to be somewhat brittle but also are markedly lacking in elongation and extensibility properties, e. g. tensile strengths of 6000'T000 lb./sq. in. and 'elongation's of 13-25%, and as high "as 50%.. On the other hand, the polyamides of this invention exhibit appreciably higher elongation properties, i. e., they can be stretched 'to'a greater degree without any loss of tensile strength while still being able to return to their original dimensions, 1. e., they arenot-permanentlyset, e. g. tensile strengths of 1500-300'0-lh/sq. in. and elongations of 50-l00%, andas high as200% "I he polyam-ides from long-chain alpha-amino acids, e. g., alpha-aminolauric and alphaaminomyristic acids while exceedingthe polyamide's of this invention. in their limpness, pliability and extensibility are markedly deficient in strength and toughness. In fact, they are relatively so weak and so soft, even to the extent of being surface marable,' thatthey ca'nnotbe usedin any of the normal film and rfiber outlets. However, the polyamides of "this invention are strong enough, tough enoughand hard enough to make them usable in the preparation of films and fibers, while at the same time, they exhibit enough of the limpness, softness, pliability and high extensibility of the fpolyamides from the longer chain alpha-amino acids to make them particularly useful in outlets requiring these properties.

The polyamide's of this invention thus'posse'ss an. unexpected combination of the desirable properties of the poiyamides from several other different types of alpha-amino acids. They exhibit a unique balance of pliability, extensibility, strength, stiffness, toughness-all properties much desired for the production of films and fibers which are strong, pliable, resilient and of good feel and hand In the preceding specification and in the following claims unit as applied to alpha-monoaminomonocarboxylic acids refers to the portion of said acid remaining after removal of an aminchydrogen and the carboxyl hydroxyl and can be conveniently represented by the general structural formula [iii] i wherein R 1S-(Ch2)nCH3 and N is 4 or 5 The foregoing detailed description has been given for clearness of understanding only and no unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described for obvious modifications will occur to those skilled in the art.

What is claimed is:

1. The N-carboanhydride of an alpha-aminon-alkanoic acid of 7 to 8 carbon atoms.

2. The N-carboanhydride of alpha-amino-nheptanoic acid.

3. The N-carboanhydride of alpha-amino-noctanoic acid.

4. A linear polyamide the recurring units of which are alpha-monoaminomonocarboxylic acid units at least 10% of which are units of the formula wherein n is an integer from 4 to 5.

5. A linear polyamide the recurring units of which are alpha-monoaminomonocarboxylic acid 10 i 7 units consisting of an aminocarboxylic acid minus an aminohydrogen and a carboxyl hydroxyl of which units at least'10% are aminocarboxyiic acid units of the formula -NH-CH-C o (CHzMCH:

wherein 11. is an integer from 4 to 5.

6. A linear polyamide the recurring units of which are alpha-monoaminomonocarboxylic acid units consisting of an aminocarboxylic acid minus an aminohydrogen and a carboxyl hydroxyl of which units at least 10% are aminocarboxylic acid units of the formula 7. A linear poiyamide the recurring units of which are alpha-monoaminomonocarboxylic acid units consisting of an aminocarboxy'lic acid minus an aminohydrogen and a carboxyl hydroxyl of which units at least 10% are aminocarboxylic acid units of the formula NH-CH-CO (CH2)5CH: CHARLES W. 'I'ULLOCK.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,293,388 Hanford Aug. 18, 1942 2,327,162 Baldwin et a1 Aug. 17, 1943 2,333,752 Ufer Nov. 9, 1943 2,352,152 Kaplan June 20', 1944 2,534,283 MacDonald Dec. 19, 1950 OTHER REFERENCES Astbury et al., Nature, Oct. 16, 1948, vol. 162,

page 596. 

1. THE N-CARBOANHYDRIDE OF AN ALPHA-AMINON-ALKONOIC ACID OF 7 TO 8 CARBON ATOMS. 